# Impact of Prescribing Cascade and Associated Drug Interaction in Alzheimer's Disease

> **NIH NIH R56** · UNIVERSITY OF HOUSTON · 2020 · $449,906

## Abstract

PROJECT SUMMARY/ABSTRACT
Dementia is a major public health concern in older adults. Alzheimer’s disease (AD) accounts for 50% to 60% of
dementia cases and nearly half of dementia-related deaths. Cholinesterase inhibitors (ChEIs) form the first line
of pharmacotherapy for AD. However, the treatment effectiveness of ChEIs is considered modest and their use
leads to adverse effects. Urinary incontinence is a prominent adverse effect of ChEI treatment, which is
commonly implicated in prescribing cascade - a clinical phenomenon where the ChEI-induced urinary
incontinence leads to prescribing of antimuscarinics. ChEIs and antimuscarinics interaction tends to nullify the
modest treatment benefit of ChEIs and can worsen AD due to the therapeutically opposing mechanism of
actions. This worsening of AD can precipitate additional cascades - prescribing of memantine for moderate-to-
severe AD, and/or antipsychotics to manage behavioral symptoms of AD, and/or may lead to Serious Adverse
Events (SAEs). Our preliminary analyses revealed that 6% of AD patients initiated antimuscarinics after ChEIs
initiation, and memantine and antipsychotics were initiated by 30% and 23% AD patients, respectively, after the
initial cascade. Although some studies have described the initial prescribing cascade of ChEIs in AD, none
of the studies have evaluated the impact of prescribing cascades due to the drug-drug interaction of ChEIs and
antimuscarinics. Therefore, the overall goal of this research is to evaluate the healthcare impact of the
prescribing cascades of ChEIs and their associated interactions among community-dwelling older adults with
AD. The specific aims of the proposed research are to: (1) examine the extent of prescribing cascades
of ChEIs in older adults with AD; and (2) assess all-cause SAEs associated with ChEI-antimuscarinic
interaction in older adults with AD. The study will involve propensity score-matched cohort design based on a
national cohort of older adults > 65 years with AD. The initial prescribing cascade of ChEIs will include initiation
of antimuscarinics. Further cascades will include initiation of memantine (for moderate-to-severe AD) and
antipsychotics (for behavioral symptoms of AD). All-cause SAEs s will include all-cause hospitalization,
emergency department visits, institutionalization, and mortality. Multi-year multistate Medicare data involving
Parts A, B, and D will be used to test the following hypotheses: (i) ChEI-antimuscarinic drug-drug interaction
leads to further cascades due to worsening of AD leading to prescribing of memantine for moderate-to-severe
AD, as well as prescription of antipsychotics to manage behavioral symptoms of AD, and (ii) there is a greater
risk for all-cause SAEs due to ChEI-antimuscarinic interaction. Concomitant ChEI-antimuscarinic users will be
compared with concomitant users of ChEIs and mirabegron, a non-anticholinergic alternative. The study will
adjust for selection bias within the multivariable context ...

## Key facts

- **NIH application ID:** 10212709
- **Project number:** 1R56AG067618-01
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Rajender R Aparasu
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,906
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212709

## Citation

> US National Institutes of Health, RePORTER application 10212709, Impact of Prescribing Cascade and Associated Drug Interaction in Alzheimer's Disease (1R56AG067618-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212709. Licensed CC0.

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